1. Design, synthesis, and activity evaluation of water-soluble propofol derivatives as anesthetic drugs.
- Author
-
Huang Y, Zhu L, Zeeshan M, Jing C, Li H, and Li W
- Subjects
- Animals, Mice, Anesthetics pharmacology, Anesthetics chemical synthesis, Anesthetics chemistry, Anesthetics, Intravenous chemistry, Anesthetics, Intravenous pharmacology, Anesthetics, Intravenous chemical synthesis, Dose-Response Relationship, Drug, Molecular Structure, Structure-Activity Relationship, Aminobutyrates chemical synthesis, Aminobutyrates chemistry, Aminobutyrates pharmacology, Drug Design, Propofol chemistry, Propofol pharmacology, Propofol chemical synthesis, Solubility, Water chemistry
- Abstract
In this work, two series of water-soluble derivatives were designed and synthesized based on the structure of propofol as the lead compound. Furthermore, the anesthetic activities of the synthesized compounds were evaluated in vivo against mice, and the in vitro propofol release rate from five target compounds was determined. The findings of this study have shown that series II compounds which possess the structure feature of propofol + γ-hydroxybutyric acid + α-aminoacetate or γ-aminobutyrate have higher therapeutic index than that of series I compounds which possess the structure feature of propofol + α-aminoacetate or β-aminopropionate. In addition, the rate of propofol released from series II compounds was significantly better than that of series I compounds. Among series II compounds, compound II-20 had a therapeutic index of 5.6 (propofol = 2.7), a duration time of 571 s (propofol = 57 s), and no significant toxicity was observed in vivo, which made it valuable for further development., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)
- Published
- 2024
- Full Text
- View/download PDF